1636P - ROS1 rearrangements and copy number alterations in NSCLC patients: High frequency of ROS1 deletions

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Lung and other Thoracic Tumours
Pathology/Molecular Biology
Presenter Sergi Clavé
Citation Annals of Oncology (2014) 25 (suppl_4): iv564-iv573. 10.1093/annonc/mdu359
Authors S. Clavé1, J. Gimeno2, S. De Muga3, L. Pijuan2, J. Vidal4, M. Lorenzo2, S. Menendez2, A. Taus5, A.M. Muñoz-Mármol6, E. Carcereny7, N. Reguart8, J.L. Mate6, S. Serrano9, J. Albanell4, B. Espinet1, E. Arriola4, M. Salido1
  • 1Pathology Department. Molecular Cytogenetic Laboratory, Hospital del Mar, 08003 - Barcelona/ES
  • 2Pathology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 3Departament De Ciències Experimentals I De La Salut Cexs, Universitat Pompeu Fabra, Barcelona/ES
  • 4Medical Oncology Department, Hospital del Mar, 8003 - Barcelona/ES
  • 5Medical Oncology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 6Pathology Department, Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 7Medical Oncology Department, Institut Català d'Oncologia. Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 8Medical Oncology Department, Hospital Clinic Barcelona, Barcelona/ES
  • 9Pathology Department, Hospital del Mar, 08003 - barcelona/ES

Abstract

Aim

Recently, c-ros oncogene 1, receptor tyrosine kinase (ROS1, 6q22) has been identified as a driver oncogene in non-small-cell lung carcinomas (NSCLC). Patients carrying ROS1 translocations are candidates to targeted therapy with crizotinib®. We aimed to determine the prevalence, patterns and fusion partners in ROS1-rearranged NSCLC samples and to characterize ROS1 copy number alterations (CNAs) by fluorescence in situ hybridization (FISH).

Methods

A total of 216 NSCLC patients (median age 64 years, 66% males, 51% smokers, 73% adenocarcinomas (ADC), 35% stage 4), were screened for ROS1 abnormalities using a break-apart FISH probe (Abbott Molecular). To characterize ROS1 partners, clones from Human 32K BAC Re-Array Library were used to develop CD74, SLC34A2 and EZR probes. Immunohistochemistry (IHC) with ROS1 D4D6 antibody (Cell Signalling Technology) was also performed in ROS1-translocated cases. Correlation with clinico-pathologic information was investigated.

Results

Four samples were ROS1 translocated (1.9%): three showed deletion of the non-translocated allele and one had a 5'ROS1 deletion. One harbored a SLC34A2-ROS1 fusion and another a CD74-ROS1. No fusion partner was identified in the other two samples. All cases were positive for ROS1 IHC staining, three presenting a cytoplasmic pattern and one with membranous pattern. ROS1-translocated tumors were ADC, all EGFR, KRAS, and ALK wt. We observed an association with non-smoking habit (P=0.036). Regarding CNAs in ROS1 non-rearranged cases, 43.5% had gains (3-6 copies) and 26.4% had deletions.

Conclusions

We confirm the low prevalence of ROS1-translocated lung ADC in a Spanish population. Moreover, our study reveals a significant frequency of ROS1 deletion as a potentially relevant aberration, also in ROS1-translocated patients.

Disclosure

All authors have declared no conflicts of interest.